Showing papers in "Hormone and Metabolic Research in 1989"
TL;DR: It was concluded that body fat distribution is more closely related to hypertension and metabolic derangements than total fat mass in the PCO syndrome.
Abstract: Anthropometric, endocrine and metabolic variables, were examined in women with polycystic ovarian syndrome (PCO), and in normal control women. Obese women with PCO had higher plasma insulin values than non obese women with PCO, but lean body mass, glucose tolerance, plasma triglycerides and blood pressure were not different in spite of almost twice the body fat mass in the obese PCO women. However, in comparisons between non-obese PCO and control women, with equal body fat mass, the PCO women had higher blood pressure, plasma triglycerides and insulin, as well as a tendency to increased lean body mass. Both PCO groups had a high waist/hip ratio and larger abdominal fat cells than controls, indicating a preferential abdominal accumulation of adipose tissue. In comparison with abdominal adipocytes, femoral adipocytes were larger and had higher lipoprotein lipase activity in the control women, while in the PCO women these regional differences were not found. Basal and norepinephrine stimulated lipolysis were higher in the abdominal than femoral adipocytes in all groups. Substitution of the PCO women with ethinyl estradiol plus desogestrel during 6 months resulted in a regression of clinical androgenic symptoms as well as a normalization of plasma concentrations of free testosterone and sex hormone binding globulin. However, neither body composition nor metabolism were normalized. It was concluded that body fat distribution is more closely related to hypertension and metabolic derangements than total fat mass in the PCO syndrome. It is suggested that the relative paucity of femoral adipose tissue is due to a lack of specific effects of progesterone on adipocytes in this region.
146 citations
86 citations
TL;DR: From an atherogenic point of view normal pregnancy seems more beneficial than pre-eclampsia, and increased concentrations of Apo A-I and HDL-C, which remained unaltered during pregnancy, may indicate a gradual change in the surface structure of the HDL particle or its subfractions.
Abstract: Serum concentrations of Apolipoprotein A-I and A-II, (Apo A-1 and Apo A-II) HDL-cholesterol (HDL-C), Total Cholesterol (TC), triglycerides (TG) and lipoprotein electrophoresis were assayed serially in the second half of normal pregnancy (21 women), in pre-eclampsia (26 women) and in both groups one and six weeks after delivery In the normal group we found increased concentrations of Apo A-I and HDL-C, which remained unaltered during pregnancy Apo A-II was unchanged Correlation coefficients for Apo A-II vs HDL-C and Apo A-I vs Apo A-II decreased gradually towards delivery while it remained at an elevated and unaltered level for Apo A-I vs HDL-C The Apo A-I/HDL-C ratio was unaltered during the whole study while the Apo A-I/A-II ratio was elevated during pregnancy and the Apo A-II/HDL-C ratio was reduced These results may indicate a gradual change in the surface structure of the HDL particle or its subfractions In pre-eclampsia Apo A-I and HDL-C concentrations were reduced, TG was increased and Apo A-II and TC were unchanged when compared with the normal pregnancy group A more pronounced correlation coefficient was recorded for Apo A-I vs HDL-C than for Apo A-II vs HDL-C and Apo A-I vs Apo II The results indicate that from an atherogenic point of view normal pregnancy seems more beneficial than pre-eclampsia
60 citations
TL;DR: The feto-maternal-hypothalamo-pituitary adrenal axis during pregnancy and delivery is investigated, in which CRH plays an important role, and significant correlations were found.
Abstract: The activity of the hypothalamo-pituitary adrenal axis was examined, by measuring the levels of immunoreactive (IR) corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol (F) in human plasma during normal pregnancy and after delivery with or without complications and during normal postpartum using a specific RIA. The level of IR-CRH in maternal plasma increased progressively during pregnancy, increased further at delivery and declined rapidly to the non-pregnant level on the 1st day postpartum. The level of IR-F in maternal plasma also increased progressively during pregnancy, increased further at delivery, but decreased slowly postpartum, not returning to the non-pregnant level within 5 days. Significant correlations were found between the level of IR-CRH and IR-ACTH, IR-CRH and IR-F, and IR-ACTH and IRF in maternal plasma both during pregnancy and after delivery. It is noteworthy that the concentration of IR-CRH in the maternal plasma at delivery was higher in multiple pregnancy than in normal pregnancy, and that the level of IR-CRH in the umbilical cord in uncomplicated cases was much lower than that in the maternal plasma, and was significantly lower than those in the umbilical cord plasma in cases of asphyxia, IUGR or premature delivery. The level of IR-F, not IR-CRH and IR-ACTH, at normal vaginal delivery was significantly higher than that at elective cesarean section. On these results, we investigated the feto-maternal-hypothalamo-pituitary adrenal axis during pregnancy and delivery, in which CRH plays an important role.
57 citations
TL;DR: Findings suggest that combination therapy may diminish the anti-hyperglycaemic action of metformin.
Abstract: Dietary fibre and biproducts of some vegetable extracts (Guar etc.) are advocated to reduce postprandial hyperglycaemia but there is some evidence that these may disturb the absorption kinetics of orally administered drugs. The effect of Guar gum on the digestive absorption of metformin was tested in 6 healthy subjects given 1700 mg of metformin with a standardised meal. Metformin blood levels showed that when given together with Guar there was a reduction in the absorption rate over the first 6 hours. These findings suggest that combination therapy may diminish the anti-hyperglycaemic action of metformin.
46 citations
42 citations
TL;DR: Serum IGF I concentration rose over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration, and one patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control.
Abstract: The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
37 citations
TL;DR: The data indicate that thyroid hormones influence pituitary-adrenal function by increasing ACTH secretion and consequently corticosterone production in Sprague-Dawley rats.
Abstract: Thyroid hormone effects on pituitary ACTH have not been well established. Adult male Sprague-Dawley rats were rendered hypo- and hyperthyroid while undergoing treatment with 6-Propylthiouracil (PTU) and L-Thyroxine (T4). At the time of decapitation, plasma values for T4 (micrograms/100 ml) were 3.9 +/- 0.4 in the control, 17.3 +/- 2.2 in the T4 and less than 2 in the PTU treated group; plasma T3 and TSH confirmed hyper- and hypothyroidism in the T4 and PTU treated groups respectively. Plasma immunoassayable ACTH and corticosterone were significantly increased in hyperthyroid and decreased in the PTU treated animals. Pituitaries were removed and incubated in DMEM. After 3 h incubation, ACTH content and secretion to the medium were significantly lower in the PTU group. As expected, pituitary TSH content and secretion were decreased in the T4 treated animals. These data indicate that thyroid hormones influence pituitary-adrenal function by increasing ACTH secretion and consequently corticosterone production.
37 citations
TL;DR: The insulin:amylase ratio of the islets compared to that in the intact pancreas was determined and indicates that the isolated islets were of a high degree of purity and may have led to the loss of glucagon and somatostatin-containing cells.
Abstract: Porcine islets were isolated by infusion of a warm collagenase solution into whole pancreata followed by static incubation at 37 degrees C for 15 minutes. The pancreata were then chopped into small pieces and the free islets purified by filtration and centrifugation over a ficoll gradient. The insulin:amylase ratio of the islets compared to that in the intact pancreas was determined in 19 pancreata and indicates that the isolated islets were of a high degree of purity. The distribution of insulin, glucagon, somatostatin and pancreatic polypeptide containing cells in pig pancreas sections was compared with that in rat. Porcine islets were much smaller and less well defined than rat islets with infiltration of acinar material even into the islet core. The levels of insulin, glucagon and somatostatin in porcine pancreas and isolated porcine islets were measured using conventional radioimmunoassay techniques. The ratio of these hormones in the pancreas was 105.1:5.8:1 respectively, and in the islets 105.1:0.68:0.087 respectively. Fragmentation of the islets during the isolation may have led to the loss of glucagon and somatostatin-containing cells. Islets cultured overnight and tested with a range of glucose concentrations for one hour did not show a significant stimulation of insulin secretion in the presence of 8.3 mM or 16.7 mM glucose compared to that in 2.8 mM glucose. However freshly isolated islets challenged with 8.3 mM, 13.9 mM and 22.2 mM glucose showed a 1.8 fold, 2.0 fold and 2.3 fold response respectively, over that in 2.8 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
35 citations
TL;DR: Data demonstrate that insulin, at low concentrations, is capable of stimulating DNA synthesis and replication of human fibroblasts through interaction with its own receptor, while at supraphysiological concentrations, much of insulin's mitogenic effect is mediated through the type I IGF receptor.
Abstract: To define the role of the insulin receptor in mediating a mitogenic response in cultured human fibroblasts, the effects of specific monoclonal antibodies against the insulin and the type I IGF receptor on insulin-stimulated [3H]thymidine incorporation were investigated. Insulin stimulated [3H]thymidine incorporation in a biphasic fashion. In the first phase, a half-maximal effect was observed at 20 ng/ml, and a seemingly maximal effect was obtained at 100-1000 ng/ml. With 10 micrograms/ml insulin, a secondary increase in [3H]thymidine incorporation was seen which was similar to the maximal effect of IGF-I. These [3H]thymidine incorporation results were corroborated with cell replication studies. MC-51, a highly specific monoclonal antibody for the insulin receptor, inhibited the stimulation of [3H]thymidine incorporation by 25 ng/ml of insulin. AlphaIR-3, a monoclonal antibody specifically directed against the type I IGF receptor, had no significant effect on insulin-stimulated [3H]thymidine incorporation at low (10-1000 ng/ml) concentrations of insulin. However, alpha IR-3 interfered with the incremental increase in [3H]thymidine incorporation observed at 10-100 micrograms/ml insulin. These data demonstrate that insulin, at low concentrations, is capable of stimulating DNA synthesis and replication of human fibroblasts through interaction with its own receptor, while at supraphysiological concentrations, much of insulin's mitogenic effect is mediated through the type I IGF receptor.
33 citations
TL;DR: Findings suggest that alpha 2- and beta-adrenergic mechanisms are involved in the hyperglycemic and hyperglucagonemic responses to SCN stimulation.
Abstract: Previously we found that in rats, electrical stimulation of the suprachiasmatic nucleus (SCN) of the hypothalamus elicited hyperglycemia associated with hyperglucagonemia without immediate hyperinsulinemia. To clarify the mechanism of these responses, we examined the effects of blockers of the autonomic nervous system on these responses. Hexamethonium, a ganglion blocker, suppressed the hyperglycemic and hyperglucagonemic responses to electrical stimulation of the SCN. Both bunazosin, an alpha 1-adrenergic blocker, and yohimbin, an alpha 2-adrenergic blocker, increased the level of insulin before stimulation, but only the latter suppressed the hyperglycemic and hyperglucagonemic responses. Propranolol, a beta-adrenergic blocker, partially inhibited the responses. These findings suggest that alpha 2- and beta-adrenergic mechanisms are involved in the hyperglycemic and hyperglucagonemic responses to SCN stimulation.
TL;DR: Pulsatile subcutaneous GnRH substitution is a successful therapeutic regimen in patients with CAHP leading to pituitary and gonadal maturation and the results of pulsatile GnRH therapy in this patient prove the hypog onadotropic hypogonadism to be of hypothalamic origin.
Abstract: Congenital adrenal hypoplasia (CAHP) in its X-linked form is associated with hypogonadotropic hypogonadism (HH). A 23 year old man with this disorder received substitution therapy with gluco- and mineralocorticoids starting one week after birth and, recently, pulsatile subcutaneous GnRH treatment via a miniature infusion pump with stepwise increasing doses from 50 to 200 ng/kg body weight/2 hours for a total of 394 days. Testosterone levels increased from prepubertal levels to 409 ng/dl after 2 weeks and to 626 ng/dl after 3 months of treatment. The results of pulsatile GnRH therapy in our patient prove the hypogonadotropic hypogonadism to be of hypothalamic origin. Pulsatile GnRH substitution is a successful therapeutic regimen in patients with CAHP leading to pituitary and gonadal maturation.
TL;DR: The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.
Abstract: Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.
TL;DR: A total of 52 patients with a primary "empty" sella syndrome underwent dynamic endocrine testing consisting of insulin-induced hypoglycaemia and a combined anterior pituitary stimulation test utilizing GnRH and TRH, finding no evidence of endocrine dysfunction.
Abstract: A total of 52 patients (38 women, 14 men) with a primary "empty" sella syndrome underwent dynamic endocrine testing consisting of insulin-induced hypoglycaemia and a combined anterior pituitary stimulation test utilizing GnRH and TRH. The diagnosis of an "empty" sella turcica was made on the basis of thin collimation CT reconstructions and in addition either metrizamide cisternography or magnetic resonance (MR) imaging. Only 16 of the patients presented with endocrine problems. Hyperprolactinaemia was the most common endocrine disturbance detected, and was found in 17 individuals. Panhypopituitarism was found in 3 patients. Nine other patients had some degree of partial pituitary insufficiency, but only two of them required replacement therapy. However, 31 patients had no evidence of endocrine dysfunction.
TL;DR: To evaluate whether the moderately elevated human growth hormone concentration, seen in insulin dependent diabetic patients, has any impact on lipoproteins,human growth hormone was given to nondiabetic persons in doses which would bring their plasma human growth hormones concentration up in the same level as seen in diabetes patients.
Abstract: To evaluate whether the moderately elevated human growth hormone concentration, seen in insulin dependent diabetic patients, has any impact on lipoproteins, human growth hormone was given to nondiabetic persons in doses which would bring their plasma human growth hormone concentration up in the same level as seen in insulin dependent diabetic patients. After one week of treatment with human growth hormone we found total plasma triglyceride to be significantly raised (0.98 mmol/l +/- 0.28 mmol/l (mean +/- SD) before versus 1.27 mmol/l +/- 0.38 mmol/l (mean +/- SD) after treatment). Very low density lipoprotein (VLDL) was separated into two fractions (VLDL-1 and VLDL-2) of which VLDL-2 is regarded as a VLDL-remnant which is suggested to be of importance for development of atherosclerosis. After one week of human growth hormone treatment there were no changes in VLDL-1 concentrations whereas a significant raise in VLDL-2 triglyceride and VLDL-2 cholesterol was seen.
TL;DR: It is suggested that in healthy subject, the decrease in oxaluria observed during fructose load reduced the product urinary [calcium] x [oxalate] which was the main factor in the genesis of urinary calcium oxalate stones while glucose load increased the risks of urolithiasis by means of the rise in both calciuria and oxAluria.
Abstract: We studied urinary calcium and oxalate excretion in response to oral fructose load and to oral glucose load each on two different randomized mornings in twelve healthy subjects. Oral fructose load provoked an increase in calciuria and a decrease in oxaluria while oral glucose load induced an increase in both calciuria and oxaluria. These results suggested that in healthy subject, the decrease in oxaluria observed during fructose load reduced the product urinary [calcium] x [oxalate] which was the main factor in the genesis of urinary calcium oxalate stones while glucose load increased the risks of urolithiasis by means of the rise in both calciuria and oxaluria.
TL;DR: The data demonstrated the existence of at least two forms of big-big hPRL in the serum and indicated that radioactive big- big h PRL may be different from these hPRls in the Sera.
Abstract: Sera from a patient with macroprolactinoma (case 1) and from a hyperprolactinemic woman with regular menstruation (case 2) were analyzed for prolactin activity by gel filtration using Sephadex G-100, Sephadex G-200 and TSK G3000SW columns. The chromatographic profile by Sephadex G-100 showed that the percentage of immunoreactive big-big hPRL was 10.7% in case 1 and 64.1% in case 2. On Sephadex G-200 and TSK G3000SW columns, the molecular weight of big-big hPRL was estimated to be more than 500,000 daltons (big-big1 hPRL) in case 1 and approximately 250,000-300,000 daltons (big-big2 hPRL) in case 2. Big-big1 hPRL in case 1 was converted to big and little hPRLs when the serum was treated with 2-mercaptoethanol (2-ME), but part of the big-big2 hPRL in case 2 was converted to a larger molecule. Radioactive big-big hPRL generated by mixing labeled hPRL with the serum from case 1 was eluted with the void volume on Sephadex G-100 column and was not converted to the other molecular forms after 2-ME treatment. There were two radioactive big-big hPRL on TSK G3000SW column and these estimated molecular weights were more than 300,000 daltons. The data demonstrated the existence of at least two forms of big-big hPRL in the serum and indicated that radioactive big-big hPRL may be different from these hPRLs in the serum.
TL;DR: The possibility of the existence of hyperthyroidism has to be considered in addition to renal damage or hyperglycemia which have already been found to increase urinary NAG.
Abstract: Urinary N-acetyl-beta-D-glucosaminidase (NAG) was measured in patients with hyperthyroidism. The value of urinary NAG in these patients was higher than that in normal subjects and diabetic patients without diabetic nephropathy. This high level of urinary NAG in patients with hyperthyroidism decreased to the level of normal subjects after treatment of hyperthyroidism. Why urinary NAG increases in the patients with hyperthyroidism remains unknown. On the occasion of estimating the significance of the high level of urinary NAG, however, the possibility of the existence of hyperthyroidism has to be considered in addition to renal damage or hyperglycemia which have already been found to increase urinary NAG.
TL;DR: The results are the first to demonstrate important roles for circadian rhythms and a direct prolactin stimulation in the regulation of lipogenesis in primary hepatocyte culture.
Abstract: Hepatocytes from male Syrian hamsters were cultured in the presence of insulin and assayed for lipogenesis by following (14C)acetate incorporation into total cell lipid at 4 hourly intervals over a 48-h period. Circadian rhythms of lipogenic activity were observed on days 2 and 3 of culture. Although the phases of the rhythms were similar, the amplitude of the peak levels of lipogenesis declined from day 2 to 3. Addition of prolactin to the culture reversed this decline when introduced at specific times relative to the lipogenic peaks. Prolactin more than doubled lipogenesis only at the daily peaks of lipogenic activity and only when added to culture 20 h before the times of peak lipogenesis. The results are the first to demonstrate important roles for circadian rhythms and a direct prolactin stimulation in the regulation of lipogenesis in primary hepatocyte culture.
TL;DR: In this paper, the effect of hypercortisolaemia on the melatonin circadian secretion of 12 patients with pituitary or adrenal dependent Cushing's syndrome and 5 healthy controls were studied.
Abstract: To determine the effect of hypercortisolaemia on the melatonin circadian secretion 12 patients with pituitary or adrenal dependent Cushing's syndrome and 5 healthy controls were studied. The melatonin circadian rhythm of secretion, observed in the control group, was abolished in the patients with hypercortisolaemia. Mean nocturnal melatonin levels and the integrated 24-hour secretion were significantly lower in the patients studied than those of the controls. Thus, in patients with Cushing's syndrome the melatonin levels are decreased and the circadian rhythm of this hormone is abolished.
TL;DR: Evidence is provided that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.
Abstract: The influence of lactate on human adipocytes lipolysis and the possible relationship between lactate-induced metabolic effects and beta-adrenoceptor binding sites were investigated. beta-sites were identified in membranes with (125I)-cyanopindolol and in intact cells with (125I)-cyanopindolol and (3H)-CGP 12177. Lactate reduced isoproterenol-induced lipolysis in a dose-response fashion and such inhibition became significant only at 16 mmol/l lactate. Exposure of human fat cells to 16 mmol/l lactate significantly reduced beta-adrenoceptors density on crude membranes. When the binding assay was performed on intact cells using (125I)-cyanopindolol at 37 degrees C, the radioligand identified the same number of receptors, regardless of the presence of lactate in the preincubation medium. When (3H)-CGP 12177 was used, it bound to about 35% less receptors in lactate pre-treated cells than in control. Seemingly, at 37 degrees C, because of its lipophilicity, (125I)-cyanopindolol can cross the plasma membrane and bind to intracellular sites whereas, (3H)-CGP 1277, due to its hydrophilicity, identifies surface receptors only. Thus, the present in vitro study provides evidence that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.
TL;DR: It seems of minor importance to define exact days of the cycle for analysing lipids and lipoproteins e.g. as controls in a study of lipid metabolism in women taking sex-hormones, for coagulation studies the cycle days may, however, be of importance.
Abstract: To examine the effects of sex-hormones on lipids, lipoproteins and coagulation in the normal menstrual cycle 37 women had blood samples taken early in the follicular phase (low estrogen) at the midcycle (high estrogen) and late in the luteal phase (high estrogen and high progesterone) under the best possible uniform and basal conditions. No significant changes (P greater than 0.05) in lipids and lipoproteins (including the HDL subfractions and apolipoproteins) were found throughout the menstrual cycle. In the coagulation system antithrombin III and factor VII did not change (P greater than 0.05). Fibrinogen, however, showed a significant (P less than 0.05) increase in the luteal phase compared to the follicular phase and midcycle. Fibrinogen showed a significant positive correlation (r = 0.2766; P less than 0.01) with progesterone, so the rise in fibrinogen in the luteal phase could be a progesterone effect. This longitudinal study performed on a large number of women under basal conditions showed that it seems of minor importance to define exact days of the cycle for analysing lipids and lipoproteins e.g. as controls in a study of lipid metabolism in women taking sex-hormones. For coagulation studies the cycle days may, however, be of importance.
TL;DR: Analysis of interaction between CsA and CT on stimulated bone resorption in the neonatal mouse calvarial resorptive system could indicate an interaction between the Cs a and CT inhibitory effects on Resorption.
Abstract: Cyclosporine A (CsA), which is a potent immunosuppressive agent, inhibits bone resorption in vitro. The inhibition of bone resorption by CsA is sustained, unlike the transient inhibition of bone resorption produced by calcitonin (CT). These different patterns of inhibition were studied by examining the interaction between CsA and CT on stimulated bone resorption in the neonatal mouse calvarial resorptive system. "Escape" from the CT inhibition of PTH stimulated bone resorption occurred after 24 hr of organ culture. Coincubation with CsA (1 micrograms/ml) delayed the "escape" response of CT + PTH treated bones, so that the full "escape" response did not occur until after 48 hr of organ culture. Likewise, a pretreatment of 24 hr with CsA (1 micrograms/ml) was sufficient to delay "escape" from CT inhibition of PTH stimulated bone resorption until after 48 hr of organ culture. A higher concentration of CsA (10 micrograms/ml) completely prevented the "escape" response. Our data could indicate an interaction between the CsA and CT inhibitory effects on resorption.
TL;DR: Significant increases in the concentration of plasma glucagon-like immunoreactivity (GLI) and plasma levels of free fatty acids (FFA) and triglycerides (TG) concomitant with decreases in circulating levels of thyroxine and triiodothyronine were observed in homing pigeons, untrained for 3 months, after a flight of 48 km lasting 90-160 min.
Abstract: Significant increases in the concentration of plasma glucagon-like immunoreactivity (GLI) and plasma levels of free fatty acids (FFA) and triglycerides (TG) concomitant with decreases in circulating levels of thyroxine (T4) and triiodothyronine (T3) and T3/T4 ratio were observed in homing pigeons, untrained for 3 months, after a flight of 48 km lasting 90-160 min. The increased level of FFA is attributed to glucagon stimulated lipolysis. The elevation of TG levels may be due to altered partitioning and utilization of lipoprotein in adipose tissue and muscle. Reductions in plasma T4, T3 and T3/T4 ratio are probably due to inhibition of T4 secretion and 5'-monodeiodination with possible conversion of T4 to reverse T3 (rT3). These processes may represent a mechanism for regulation of thyroid hormone metabolism during strenuous and extended flight.
TL;DR: It is concluded that Hb produces a dose-dependent and reversible inhibition of cartilage growth and may contribute to the growth retardation associated with chronic hemolytic conditions.
Abstract: Growth retardation is a feature of several diseases associated with chronic hemolysis (i.e., uremia and the hemoglobinopathies). Although the growth failure is undoubtedly multifactorial, circulating hemoglobin (Hb) may inhibit cartilage growth directly. We tested this hypothesis using the hypophysectomized rat costal cartilage sulfation bioassay and the embryonic chicken pelvic rudiment bioassay, both very sensitive to growth factors and growth inhibitors. In the rat bioassay, Hb produced a dose-dependent inhibition of both basal and normal rat serum (NRS)-stimulated 35SO4 uptake. In the chick bioassay, NRS stimulated cartilage growth as expected, but Hb severely inhibited both basal and NRS-stimulated growth. However, after the cartilages were preincubated with Hb for 2 days, subsequent exposure to NRS allowed them to resume growth at the same rate as cartilage exposed to NRS for the entire 5 days. The growth inhibition could be accounted for by the heme contained in Hb. We conclude that Hb produces a dose-dependent and reversible inhibition of cartilage growth and may contribute to the growth retardation associated with chronic hemolytic conditions.
TL;DR: The data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.
Abstract: To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.